US11566071B2ActiveUtilityA1
Nucleic acid molecules encoding anti-GPRC5D antibodies
Assignee: MEMORIAL SLOAN KETTERING CANCER CENTERPriority: Dec 5, 2014Filed: Dec 31, 2019Granted: Jan 31, 2023
Est. expiryDec 5, 2034(~8.4 yrs left)· nominal 20-yr term from priority
C07K 2317/34C07K 16/2809A61K 47/6849C07K 2317/622G01N 33/6872C07K 2319/21C07K 2317/92C07K 2317/24C07K 2317/21A61P 35/00C07K 16/28C07K 2317/31G01N 2333/705G01N 2333/7051C07K 2317/73A61K 47/6803G01N 33/6893C07K 16/2863
85
PatentIndex Score
2
Cited by
245
References
35
Claims
Abstract
The presently disclosed subject matter provides antibodies that bind to GPRC5D and methods of using the same.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A nucleic acid molecule encoding an anti-human G-protein coupled receptor family C group 5 member D (GPRC5D) antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:130, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:131, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:132; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:133, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:134, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:135;
(ii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:142, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:143, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:144; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:145, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:147;
(iii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:154, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:155, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:156; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:157, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:158, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:159;
(iv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:160, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:161, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:162; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:163, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:164, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:165;
(v) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:166, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:167, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:168; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:169, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:170, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:171;
(vi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:172, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:173, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:174; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:175, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:176, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:177;
(vii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:178, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:179, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:180;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:181, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:182, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:183;
(viii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:184, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:185, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:186; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:187, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:188, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:189;
(ix) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:190, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:191, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:192; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:193, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:194, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:195;
(x) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:196, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:197, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:198; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:199, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:200, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:201;
(xi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:202, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:203, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:204; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:205, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:206, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:207;
(xii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:208, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:209, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:210; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:211, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:212, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:213;
(xiii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:214, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:215, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:216; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:217, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:218, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:219;
(xiv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:220, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:221, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:222; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:223, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:224, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:225;
(xv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:226, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:227, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:228; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:229, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:230, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:231;
(xvi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:232, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:233, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:234; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:235, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:236, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:237;
(xvii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:238, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:239, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:240; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:241, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:242, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:243;
(xviii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:244, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:245, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:246; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:247, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:248, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:249;
(xix) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:250, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:251, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:252; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:253, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:254, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:255;
(xx) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:256, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:257, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:258; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:259, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:260, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:261;
(xxi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:262, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:263, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:264; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:265, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:266, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:267;
(xxii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:292, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:293, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:294; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:295, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:296, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:297;
(xxiii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:303, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:304, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:305; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:306, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:307, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:308;
(xxiv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:316, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:317, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:318; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:319, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:320, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:321;
(xxv) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:328, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:329, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:330; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:331, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:332, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:333;
(xxvi) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:340, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:341, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:342; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:343, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:344, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:345; or
(xxvii) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:352, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:353, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:354; and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:355, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:356, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:357.
2. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:202, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:203, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:204; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:205, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:206, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:207.
3. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:208, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:209, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:210; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:211, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:212, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:213.
4. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:214, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:215, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:216; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:217, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:218, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:219.
5. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:220, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:221, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:222; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:223, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:224, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:225.
6. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:226, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:227, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:228; and the light chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:229, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:230, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:231.
7. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:5, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:25, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:45, SEQ ID NO:49, SEQ ID NO:53, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:73, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:85, SEQ ID NO:89, SEQ ID NO:93, SEQ ID NO:298, SEQ ID NO:310, SEQ ID NO:322, SEQ ID NO:334, SEQ ID NO:346, or SEQ ID NO:358.
8. The nucleic acid molecule of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:6, SEQ ID NO:14, SEQ ID NO:22, SEQ ID NO:26, SEQ ID NO:30, SEQ ID NO:34, SEQ ID NO:38, SEQ ID NO:42, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:54, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:86, SEQ ID NO:90, SEQ ID NO:94, SEQ ID NO:299, SEQ ID NO:311, SEQ ID NO:323, SEQ ID NO:335, SEQ ID NO:347, or SEQ ID NO:359.
9. The nucleic acid molecule of claim 1 , wherein:
(a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:5, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:25, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:45, SEQ ID NO:49, SEQ ID NO:53, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:73, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:85, SEQ ID NO:89, SEQ ID NO:93, SEQ ID NO:298, SEQ ID NO:310, SEQ ID NO:322, SEQ ID NO:334, SEQ ID NO:346, or SEQ ID NO:358; and
(b) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:6, SEQ ID NO:14, SEQ ID NO:22, SEQ ID NO:26, SEQ ID NO:30, SEQ ID NO:34, SEQ ID NO:38, SEQ ID NO:42, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:54, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:86, SEQ ID NO:90, SEQ ID NO:94, SEQ ID NO:299, SEQ ID NO:311, SEQ ID NO:323, SEQ ID NO:335, SEQ ID NO:347, or SEQ ID NO:359.
10. The nucleic acid molecule of claim 1 , wherein:
(i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:5, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:6;
(ii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:13, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:14;
(iii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:22;
(iv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:25, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:26;
(v) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:29, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:30;
(vi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:33, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:34;
(vii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:37, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:38;
(viii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:41, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:42;
(ix) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:45, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:46;
(x) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:49, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:50;
(xi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54;
(xii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:57, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:58;
(xiii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:62;
(xiv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66;
(xv) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:70;
(xvi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:74;
(xvii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:77, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:78;
(xviii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:81, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:82;
(xix) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:86;
(xx) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:90;
(xxi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:93, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:94;
(xxii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:298, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:299;
(xxiii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:310, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:311;
(xxix) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:322, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:323;
(xxv) the heavy chain variable region comprises amino acids the sequence set forth in SEQ ID NO:334, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:335;
(xxvi) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:346, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:347; or
(xxvii) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:358, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:359.
11. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:54.
12. The nucleic acid molecule of claim 11 , wherein the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv).
13. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:57, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:58.
14. The nucleic acid molecule of claim 13 , wherein the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv).
15. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:62.
16. The nucleic acid molecule of claim 15 , wherein the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv).
17. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:66.
18. The nucleic acid molecule of claim 17 , wherein the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv).
19. The nucleic acid molecule of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:70.
20. The nucleic acid molecule of claim 19 , wherein the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv).
21. The nucleic acid molecule of claim 1 , wherein the antibody or antigen-binding fragment thereof is fully human.
22. The nucleic acid molecule of claim 1 , wherein the antibody or antigen-binding fragment thereof is chimeric or humanized.
23. The nucleic acid molecule of claim 1 , wherein the antibody or antigen-binding fragment thereof is a Fab, a Fab′, a F(ab′) 2 , a variable fragment (Fv), or a single chain variable fragment (scFv).
24. The nucleic acid molecule of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO: 105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:300, SEQ ID NO:312, SEQ ID NO:324, SEQ ID NO:336, SEQ ID NO:348, or SEQ ID NO:360.
25. The nucleic acid molecule of claim 1 , wherein the antibody or antigen-binding fragment thereof binds to human GPRC5D with a binding affinity (K d ) of from about 1×10 −9 M to about 1×10 −8 M.
26. A nucleic acid molecule encoding an anti-human G-protein coupled receptor family C group 5 member D (GPRC5D) antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
(a) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:5, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:25, SEQ ID NO:29, SEQ ID NO:33, SEQ ID NO:37, SEQ ID NO:41, SEQ ID NO:45, SEQ ID NO:49, SEQ ID NO:53, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:73, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:85, SEQ ID NO:89, SEQ ID NO:93, SEQ ID NO:298, SEQ ID NO:310, SEQ ID NO:322, SEQ ID NO:334, SEQ ID NO:346, or SEQ ID NO:358; and
(b) a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:6, SEQ ID NO:14, SEQ ID NO:22, SEQ ID NO:26, SEQ ID NO:30, SEQ ID NO:34, SEQ ID NO:38, SEQ ID NO:42, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:54, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:74, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:86, SEQ ID NO:90, SEQ ID NO:94, SEQ ID NO:299, SEQ ID NO:311, SEQ ID NO:323, SEQ ID NO:335, SEQ ID NO:347, or SEQ ID NO:359.
27. The nucleic acid molecule of claim 26 , wherein the heavy chain variable region and the light chain variable region are selected from the group consisting of:
(i) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:5, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:6;
(ii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:13, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:14;
(iii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:21, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:22;
(iv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:25, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:26;
(v) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:29, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:30;
(vi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:33, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:34;
(vii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:37, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:38;
(viii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:41, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:42;
(ix) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:45, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:46;
(x) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:49, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:50;
(xi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:53, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:54;
(xii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:57, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:58;
(xiii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:61, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:62;
(xiv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:65, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:66;
(xv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:69, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:70;
(xvi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:73, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:74;
(xvii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:77, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:78;
(xviii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:81, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:82;
(xix) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:85, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:86;
(xx) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:89, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:90;
(xxi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:93, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:94;
(xxii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:298, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:299;
(xxiii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:310, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:311;
(xxix) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:322, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:323;
(xxv) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:334, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:335;
(xxvi) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:346, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:347; and
(xxvii) a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 of the heavy chain variable region sequence set forth in SEQ ID NO:358, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 of the light chain variable region sequence set forth in SEQ ID NO:359.
28. The nucleic acid molecule of claim 26 , wherein the antibody or antigen-binding fragment thereof is fully human.
29. The nucleic acid molecule of claim 26 , wherein the antibody or antigen-binding fragment thereof is chimeric or humanized.
30. The nucleic acid molecule of claim 26 , wherein the antibody or antigen-binding fragment thereof is a Fab, a Fab′, a F(ab′) 2 , a variable fragment (Fv), or a single chain variable fragment (scFv).
31. The nucleic acid molecule of claim 26 , wherein the antibody or antigen-binding fragment thereof binds to human GPRC5D with a binding affinity (K d ) of from about 1×10 −9 M to about 1×10 −8 M.
32. An expression vector comprising the nucleic acid molecule of claim 1 .
33. A host cell comprising the nucleic acid molecule of claim 1 .
34. An expression vector comprising the nucleic acid molecule of claim 26 .
35. A host cell comprising the nucleic acid molecule of claim 26 .Cited by (0)
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